Content developed by Marie Fuzzati (IRCCS Mondino Foundation and France Parkinson) and Ludivine Breger (INSERM), in close collaboration with MIUR. For more information or for questions, please contact experimentalmodels@jpnd.eu.

General Information

Mouse: Originally in 129/Sv-SL mice; crossed and maintained on C57BL/6

Mice with a homozygous disruption in the promoter region of the Pitx3 homeogene leading to loss of protein expression (Pitx3-/-).

14 weeks: significant reduction of TH-positive neurons (72%) is observed in the SN , with the exemption of the dorsal tier of the SN (dSNc), as well as in the VTA (52%). Interestingly, in wild type mice TH-positive neurons in the dSNc do not express Pitx3. This indicates the existence of different subpopulations of TH-positive neurons in the SN that display different intrinsic requirements (presence of PitX3) for survival. Sparing of dSNc in the mutant mice is reminiscent of observations in PD brain samples.

Inclusions

Not reported

Motor Behaviours

1 months and 4 weeks: a reduction in ambulatory and stereotypic activities is observed during the night , reminiscent of PD akinesia; no reduction is detected during the day. This reduction is not due to the blindness associated with the mutation.

Response to dopaminergic treatment

Non motor Behaviours

Social transmission of food preference: this task is thought to involve cholinergic circuit in the brain and is normal in aphakia mice.

Avoidance learning: the change in latency to avoid a shock is reduced in mutant mice, indicating an impaired memory for the shock.

Swimming T-maze: after training aphakia mice display an increased latency to find the platform suggesting an impairment in procedural learning. Because this test is physically demanding and may be influenced by motor impairments the dry, food-motivated T-maze was also performed (see below).

Dry T-maze : aphakia mice do not learn where the food is located with training. This observation confirms the swimming T-maze data and indicates a reduced procedural learning capacity.

Anhedonia:depression-like symptoms, evidenced using the sucrose preference test is observed in aphasia mice (10-16 weeks). This symptom is reversed by chronic treatment with an anticholinergic antidepressant (imipramine).

Electrophysiology

3-5 months: fast-scan cyclic voltametric measurement indicate that the peak magnitude of the single pulse-evoked dopamine signal is 92% smaller in aphakia mice compared with control mice .

Neuroinflammation

Your email address will not be published. Required fields are marked *

Comment

Name *

Email *

Website

Save my name, email, and website in this browser for the next time I comment.

Notify me of followup comments via e-mail. You can also subscribe without commenting.

The EU Joint Programme – Neurodegenerative Disease Research (JPND) is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases, in particular Alzheimer’s. Learn More